Project IV - David Sept, Ph.D. Title: An Informatics Resource for Targeted Nanoparticle Therapeutics Each year, many billions of dollars are spent on the development and testing of new drugs for the treatment of cancer. Although these compounds perform well in pre-trial in vitro screens, their failure in vivo is typically attributed to problems with toxicity originating from misdistribution, cross-reactivity, or non-specific accumulation at other sites. Targeted delivery of high affinity drugs using nanoparticles promises to alleviate many of these difficulties;however, there are still many unknowns with respect to the physical and pharmacological properties of such nanoscale therapeutics. The focus of this project is to develop a nanoparticle informatics resource that will include a comprehensive taxonomical database of available technologies and a toolbox for pharmacokinetics and pharmacodynamics modeling of nanoparticles. This resource will be developed by a team of three computational biologists (Baker, Pappu, and Sept). It will collate information relevant to the pharmacological behavior of these nanoparticles, including the uptake, degradation and clearance of these particles, as well as the ability to conjugate each particle with binding ligands and small molecules. Additionally, the resource will develop and apply both pharmacokinetics and pharmacodynamics models to simulate the workings of targeted nanoparticles as drug delivery agents. By providing a comprehensive and centralized resource for such information, this resource will allow researchers from either the nanoscience or pharmaceutical side to find compatible technologies and solutions that will enable their product to be used in the treatment, diagnosis or prevention of cancer. In this manner, this project will directly facilitate the development of nanoparticle technologies;particularly those in Projects I - III within this SCCNE proposal.